1. Field of the Invention
This invention relates to a process for producing electron deficient olefins, such as 2-cyanoacrylates, in a polar solvent, such as an ionic liquid.
2. Brief Description of Related Technology
Cyanoacrylate adhesives are known for their fast adhesion and ability to bond a wide variety of substrates. They are marketed as “super glue” type adhesives. They are useful as an all-purpose adhesive since they are a single component adhesive, very economical as only a small amount will do, and generally do not require any equipment to effectuate curing.
Traditionally, cyanoacrylate monomers are produced by way of a Knoevenagel condensation reaction between a formaldehyde precursor, such as paraformaldehyde, and an alkyl cyanoacetate with a basic catalyst. During the reaction, monomer forms and polymerises in situ to a prepolymer that is subsequently thermally cracked or depolymerised into the pure constituent monomer. This approach has remained essentially the same although various improvements and variants have been more recently introduced. See e.g. U.S. Pat. Nos. 6,245,933, 5,624,699, 4,364,876, 2,721,858, 2,763,677 and 2,756,251.
In U.S. Pat. No. 3,142,698, the synthesis of difunctional cyanoacrylates using a Knoevenagel condensation is described. However the ability to thermally depolyerise the resulting, now crosslinked, prepolymer in a reliable and reproducible manner to produce pure difunctional monomers in high yields is questionable [see J. Buck, J. Polym. Sci., Polym. Chem. Ed., 16, 2475-2507 (1978), and U.S. Pat. Nos. 3,975,422, 3,903,055, 4,003,942, 4,012,402, and 4,013,703].
A variety of other processes for producing cyanoacrylate are known, and some of which are described below.
U.S. Pat. No. 5,703,267 defines a process for producing a 2-cyanoacrylic acid which comprises subjecting a 2-cyanoacrylate and an organic acid to a transesterification reaction.
U.S. Pat. No. 5,455,369 defines an improvement in a process for preparing methyl cyanoacrylate, in which methyl cyanoacetate is reacted with formaldehyde to form a polymer that is then depolymerized to the monomeric product, and in which the purity of yield is 96% or better. The improvement of the '369 patent is reported to be conducting the process in a poly(ethyelene glycol) diacetate, dipropionate, or dibutyrate, having a number average molecular weight of 200-400, as the solvent.
U.S. Pat. No. 6,096,848 defines a process for the production of a biscyanoacrylate, which comprises the steps of esterifying a 2-cyanoacrylic acid or transesterifying an alkyl ester thereof to obtain a reaction mixture; and fractionally crystallizing the reaction mixture to obtain the biscyanoacrylate.
U.S. Pat. No. 4,587,059 defines a process for the preparation of monomeric 2-cyanoacrylates comprising the steps of (a) reacting (i) a 2,4-dicyanoglutarate with (ii) formaldehyde, cyclic or linear polymers of formaldehyde, or a mixture thereof, in the presence of between about 0.5 and about 5 mols of water per mol of 2,4-dicyanoglutarate, at an acid pH of about 3 to slightly less than 7, and at a temperature of about 70 to about 140, to form an oligomeric intermediate product, and (b) removing water that is present from step (a) and thermolyzing the oligomeric intermediate product for a period of time sufficient to effect its conversion to monomeric 2-cyanoacrylates.
Commercial production of cyanoacrylate monomers ordinarily relies on the depolymerisation of a prepolymer formed under Knoevenagel reaction conditions. Previous efforts to produce cyanoacrylates explored alternative routes that do not rely on depolymerisation, for instance in the synthesis of difunctional monomers that cannot be reliably accessed by depolymerisation, or for the synthesis of esters not easily accessed by depolymerisation.
Still today the Knoevenagel condensation reaction is believed to remain the most efficient and prevalent commercial method for producing high yields of monofunctional cyanoacrylates. Nevertheless, it would be desirable to not have to resort to thermally induced depolymerisation of a prepolymer produced by the Knoevenagel condensation reaction. This prospect would also enable facile access to highly useful difunctional monomers, such as so-called bis-cyanoacrylates or hybrid materials of cyanoacrylate and other polymerisable or reactive functions.
The Knoevenagel reaction is well known not only for its usefulness in the manufacture of cyanoacrylates, but also (and perhaps more so) for its immense potential generally in the synthesis of electrophilic olefins from active methylene and carbonyl compounds [G. Jones, Organic Reactions, Vol. XV, 204, Wiley, New York (1967)]. A wide range of catalysts have been employed in carrying out this reaction, each affording variable yields of olefins. The reaction is catalysed by weak bases under homogeneous conditions. More recently, heterogeneous catalysts have been use, many of which include inorganic materials such as clays and zeolites [F. Bigi et al., J. Org. Chem., 64, 1033 (1999)]. These materials are environmentally benign and have been used because they are ditopic in nature, some containing both acidic and basic sites, while others are soley acidic or soley basic. Some Lewis acid catalysts have also been employed in the Knoevenagel reaction [B. Green et al., J. Org. Chem., 50, 640 (1985); P. Rao et al., Tett. Lett., 32, 5821 (1991)]. Since bases are generally active nucleophiles and cyanoacrylate monomer is highly susceptible to initiation of polymerisation by active nucleophiles, it is not possible to exploit base catalysed Knoevenagel synthesis of cyanoacrylate monomer without polymerisation occurring. And while acid catalysed Knoevenagel condensation reactions to form cyanopentadienoate monomers (related to cyanoacrylates) are known (see e.g. U.S. Pat. No. 6,291,544), these routes do not lead to the direct synthesis of cyanoacrylate monomers per se.
The Knoevenagel reaction also liberates water during the condensation of aldehydes with reactive methylene compounds, and neutral and basic water is well known to initiate polymerisation of cyanoacrylate monomers.
The efficiency of the Knoevenagel reaction is also known to be highly solvent dependent and that usually dipolar aprotic solvents, like dimethylformamide or dimethylsulfoxide, or especially useful in this condensation, because the second step, a 1,2-elimination has been reported to be inhibited by protic solvents [L. Tietze and U. Beifuss, Comprehensive Organic Synthesis, B. Trost et al., eds., Pergamon Press, Oxford, Vol. 2, Chapter 1.11, 341 (1991)]. The aforementioned solvents are toxic, teratogenic and suspected carcinogens, and can initiate cyanoacrylate polymerisation, thus their usage is disfavoured on a commercial scale.
Notwithstanding the reported inhibition by protic solvents, various authors have found that the Knoevenagel reaction easily occurs in protic media and also in water, even though this reaction remarkably involves a net dehydration [see e.g. F. Bigi et al., J. Org. Chem., 64, 1033 (1999), P. Laszlo, Ac Chem. Res., 19, 121 (1986), K. Kloestra et al., J. Chem. Soc., Chem. Commun., 1005 (1995), P. Lednor et al., J. Chem. Soc., Chem. Commun., 1625 (1991), and F. Bigi et al., Tett. Lett., 40, 3465 (1999)].
Recently there have been reports of the use of polar aprotic and protic solvents, including water, in uncatalysed Knoevenagel reactions leading to excellent yields and selectivities in the formation of products dervied from malononitrile and mainly aromatic aldehydes, although some aliphatic aledhehydes were reported on [F. Bigi et al., Green Chem., 2, 101 (2000)]. The use of water as a solvent in organic chemistry has received increasing attention in the past decade [see e.g. R. Breslow, Ac Chem. Res., 24, 159 (1991) and Li, Chem. Rev., 93, 2023 (1993)], however a large excess of neutral and basic aqueous reaction media would initiate polymerisation in the Knoevenagel synthesis of cyanoacrylate monomers even though this may offer other benefits since water is an environmentally benign, non flammable, and relatively inexpensive solvent. Thus a depolymerisation step is still required to yield pure monomer.
A highly desirable goal would be to find a solvent with some of the characteristics of water that would encourage high yields and selectivities and preferably act as a solvent-catalyst for the Knoevenagel reaction of electron deficient olefins, such as cyanoacrylates, without resort to a depolymerisation step. If necessary, acidic (e.g. Lewis) catalysts may be used in conjunction with such a solvent, as could common dehydrating agents that would react with water liberated from the Knoevenagel reaction proper.
Several publications have shown that replacing organic solvents by ionic liquids can lead to improvements in well known procedures [T. Welton, Chem Rev., 99, 2071 (1999), D. Morrison et al., Tet. Lett., 42, 6053 and 6097 (2001), and M. Smietana et al., Org. Lett., 3, 1037 (2001)]. Indeed, ionic liquids have been used with some success as solvents in Knoevenagel reactions. For example, n-butyl pyridinium nitrate has been used as a solvent to replace conventional organic solvents in the Knoevenagel condensation of various carbonyl substrates with active methylene compounds [Y-Q Li et al., Chinese Chem. Letts., 14, 5, 448 (2003)]. The ionic liquid, 1-butyl-3-methylimidiazolium chloroaluminate, has been used in the synthesis of electrophilic alkenes via the Knoevenagel condensation [J. Harjani et al., Tet. Lett., 43, 1127 (2002)]. Functionalised ionic liquid solvents have also been used in Knoevenagel reactions [X-M Xu et al., J. Org. Chem., 24(10), 1253 (2004)]. The use of ionic liquids as solvents for Knoevenagel condensation in the presence of specific catalysts for this reaction is also known [Su et al., Synthesis, 4, 555 (2003)].
Recently, J. S. Yadav et al., Phosphane-Catalyzed Knoevenagel Condensation: A Facile Synthesis of α-Cyanoacrylates and α-Cyanonitriles”, Eur. J. Org. Chem., 546-551 (2004) reports of the use of triphenylphosphane [sic, triphenylphosphine] as a catalyst for the Knoevenagel condensation of aldehydes with acidic methylene compounds, such as ethyl cyanoacetate and malonitrile, to afford substituted olefins in an efficient manner under mild and solvent-free conditions. Triphenyphosphine is a known initiator for the polymerization of 2-cyanoacrylates.
However, to date, it is not believed that any one has investigated the synthesis of cyanoacrylates or other electron deficient olefins using an ionic liquid as a solvent in the Knoevenagel condensation reaction.